REGULATION OF GENE EXPRESSION BY EUKARYOTES Gene expression

REGULATION OF GENE EXPRESSION BY EUKARYOTES

Gene expression in eukaryotic cells • Typical human cell: only 20% of genes expressed at any given time • Different cell types (with identical genomes) turn on different genes to carry out different functions • Differences between cell types is due to differential gene expression

Eukaryotic gene expression regulated at different stages

First stage: At the DNA level Chromatin Structure: • Tightly bound DNA less accessible for transcription

First stage: At the DNA level • DNA methylation: - Methyl groups are added to the DNA molecule - Changes the activity of a DNA segment without changing the sequence - When located in a gene promoter, it typically acts to repress gene transcription

First stage: At the DNA level • Histone acetylation: - acetyl groups added to histones; - Chromatin loosened; transcription

Epigenetic Inheritance • Epigenome: - All of the chemical compounds that have been added to the entirety of one’s DNA - Not part of the DNA sequence - Can be inherited through the generations

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Second stage: At the transcription level Transcription Initiation: • Specific transcription factors (activators or repressors) bind to control elements (enhancer region) • Activators: increase transcription • Repressors: decrease transcription

Transcription Initiation Complex • • • TATA box: attracts transcription factors Transcription factors: attracts RNA Polymerase Enhancer: A DNA region that can be bound by activators/repressor to increase/decrease transcription

Cell type-specific transcription • A particular combination of control elements can activate transcription only when the appropriate activator proteins are present

Third stage: At the post transcriptional level • Alternate splicing of RNA - Makes it possible for a single gene to encode several polypeptide • Initiation of translation - Can be blocked by regulatory proteins that binds to sequences or structures of the m. RNA • After translation - Various types of protein processing, including cleavage and chemical modification

Alternate Splicing • A prominent mechanism to generate protein diversity • Takes place within the nucleus either during or immediately after transcription • Particular exons of a gene may be included within or excluded from the final m. RNA

Third stage: At the post transcriptional level Regulation of m. RNA: • Micro RNA (mi. RNA): Inhibit translation of m. RNA • Small interfering RNA (si. RNA): Cleave m. RNA

Prokaryotic Vs. Eukaryotic • Prokaryotic - Transcription in cytoplasm - Uses operon as functional units - Regulatory gene makes repressor - DNA m. RNA Protein - One m. RNA codes for several proteins (Polycistronic) • Eukaryotic - Transcription in nucleus - Uses transcription factors - Regulatory gene are bound by various transcription factors - DNA Prem. RNA Protein - One m. RNA codes for one protein